Vascular inflammation and oxidative stress are fast becoming key components of aging science. However, the interaction been these two entities is often not addressed in current research. To address these issues, a basic understanding of the pathophysiology of oxidative stress and vascular inflammation that results in vaso-occlusion is required. Closing this gap in knowledge will be the focus of this proposal. We will examine the link between hemolysis, oxidative stress, vascular inflammation and vaso-occlusion during aging using sickle cell disease as a model. We will learn from nature's protective response to excessive heme burden, the induction of HO-1. We will modulate HO-1 to decrease oxidative stress and vascular inflammation and prevent vaso-occlusion. New therapies which can decrease oxidative stress and vascular inflammation will result from these studies. Preventing vaso-occlusion will protect organ function, improve quality of life, and reduce morbidity and mortality. This proposal supports the mission of NIA by its focus on research that will develop and evaluate innovative treatments related to the prevention and treatment of oxidative stress and vascular inflammation. This proposal will advance the field by providing a clear understanding of the link between hemolysis, vascular inflammation, oxidative stress, and vaso-occlusion.